Figure 1. Development of nTregs and iTregs and the relevant markers associated with each.

nTregs (top) differentiate from naïve conventional T cells to Foxp3⁺ Tregs in the thymus. In the periphery, natural Tregs express a number of cell surface markers, indicated in the box below the depiction of the natural Treg. However, none of these cell surface markers are unique to Tregs as they are also found on activated conventional T cells. Natural Tregs utilize the cytokines IL-10, IL-35 and TGFβ to exert their suppressive effects upon conventional T cells. TGFβ and IL-2 have also been shown to be important to the maintenance and fidelity of the Treg signature. iTregs (bottom) can be generated from conventional T cell precursors. Once in the periphery, naïve conventional T cells can be induced to become Foxp3⁻ Tr1 cells or Foxp3⁺ Th3 cells via IL-10 and/or TGFβ secreted by APCs such as dendritic cells and macrophages. These induced Tregs share similar cell surface markers as natural Tregs. Foxp3⁺ induced Tregs can accumulate in the gut through upregulation of CCR9 and α4β7 via TGFβ and retinoic acid produced by CD103⁺ dendritic cells. TEC= thymic epithelial cell; T_conv= conventional T cell; DC= dendritic cell; RA= retinoic acid